Sherwin Catherine M T, Wead Stephanie, Stockmann Chris, Healy Daniel, Spigarelli Michael G, Neely Alice, Kagan Richard
Division of Clinical Pharmacology, Department of Paediatrics, University of Utah School of Medicine, Salt Lake City, Utah, United States.
James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, United States.
Burns. 2014 Mar;40(2):311-8. doi: 10.1016/j.burns.2013.06.015. Epub 2013 Jul 19.
The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.
Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10-20mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.
The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean Cmax was 33.2±9.4μg/mL and the mean Cmin was 3.8±4.6μg/mL. The final covariate model estimated clearance as 5.98L/h/70kg (4.97-6.99, 95% CI), the volume of distribution in the central compartment as 16.7L/70kg (14.0-19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1L/70kg (15.0-80.4, 95% CI), and the inter-compartmental clearance as 3.38L/h/70kg (2.44-4.32, 95% CI). In multivariate analyses, current weight (P<0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.
Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients.
本研究的目的是：（1）确定重度烧伤儿童中阿米卡星的药代动力学；（2）识别有影响的协变量。
在NONMEM 7.2中对住院儿童进行群体药代动力学建模，这些儿童接受10 - 20mg/kg的阿米卡星，每天分两次、三次或四次给药，作为疑似烧伤相关败血症早期经验性治疗的一部分。
分析纳入了70例患者（6个月至17岁）的282个阿米卡星血清浓度数据。阿米卡星的平均Cmax为33.2±9.4μg/mL，平均Cmin为3.8±4.6μg/mL。最终的协变量模型估计清除率为5.98L/h/70kg（4.97 - 6.99，95%置信区间），中央室分布容积为16.7L/70kg（14.0 - 19.4，95%置信区间），外周室分布容积为40.1L/70kg（15.0 - 80.4，95%置信区间），以及室间清除率为3.38L/h/70kg（2.44 - 4.32，95%置信区间）。在多变量分析中，当前体重（P<0.001）是一个显著的协变量，而年龄、性别、身高、血清肌酐、C反应蛋白、血小板计数、烧伤的范围和类型以及同时使用万古霉素均不影响阿米卡星的药代动力学。
与健康成年志愿者相比，烧伤儿童的阿米卡星清除率升高。然而，阿米卡星的峰值浓度与其他危重症儿童所达到的浓度相当，这表明阿米卡星清除率升高可能不会导致抗菌效果低于治疗水平。在本研究中，我们发现阿米卡星呈现二室药代动力学，体重对阿米卡星清除率有强烈影响。需要进一步的药效学研究来确定儿科烧伤患者中阿米卡星的最佳给药方案。
